Emulsion comprising a gelled anionic hydrocolloid aqueous outer phase, a non-aqueous intermediate phase and an aqueous inner phase

ABSTRACT

The invention relates to an emulsion comprising an aqueous gelled outer phase, a non-aqueous intermediate phase and an inner phase containing an active ingredient incompatible with the gelled outer phase, wherein the outer phase comprises one or more anionic hydrocolloids in an amount of 0.1% to 5% by weight of the weight of the outer phase, the intermediate phase comprises an oil, and the inner phase containing the active ingredient is encapsulated by the intermediate phase. The emulsions are useful for the preparation of antiperspirants, sustained release drug formulations or personal hygiene products.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention is concerned with an emulsion, a method ofpreparing the same and its use, and in particular an emulsion comprisinga gelled outer phase having an active ingredient dispersed therein.

2. Description of the Related Art

Encapsulation of active ingredients in gels, such as gellan gum, is wellknown. For example, JP 62125850 discloses encapsulation of ingredients,such as food, oils, medicines and the like, within beads of gellan gum.In an example, a salad oil emulsion was added as 0.5 ml size drops to a1% gellan gum solution. The resulting beads had a 0.35 mm thick skin andcontained 0.3 ml of oil in each sphere.

U.S. Pat. No. 4,563,366 discloses a gelled food product which comprisesa matrix containing at least one dispersed food ingredient whichcomprises vegetable, fruit, meat, fish, sugar, and/or milk.

GB2219803 discloses a gelling composition which comprises a blend ofgellan, kappa-carrageenan and mannan. The gelling composition is usefulas a gelling matrix in food products such as pet foods and the like.

JP 63267361 discloses a gel which can contain fragrances, microbicides,insecticides, and the like, in addition to a gelation agent selectedfrom gellan gum, and its combination with carrageenan, gelatin, agar,locust bean gum, xanthan gum, carboxymethyl cellulose and the like.

Incorporation of certain active ingredients in gel matrices comprisinganionic hydrocolloids, such as gellan gum, has however proved to beproblematic due to the incompatibility of the active ingredients withthe gels causing degredation or precipitation of the latter.

This incompatibility can be seen, for example, when aluminiumchlorohydrate is blended with gellan gum in an attempt to prepare anantiperspirant, whereby undesirable precipitation of the gellan gumoccurs. Similarly, the incompatibility of other cationic ingredients,such as cationic drugs (verapamil hydrochloride, chloropheniraminemaleate and the like) and cationic surfactants (such as benzalkoniumchlorides and the like) with the above-mentioned anionic gel matriceshas proven to be problematic.

SUMMARY OF THE INVENTION

The present invention alleviates the above problem, wherein activeingredients incompatible with a gel matrix can be incorporated thereinwithout adversely affecting the properties of the gel.

According to the present invention there is provided an emulsioncomprising an aqueous gelled outer phase, a non-aqueous intermediatephase and an aqueous inner phase containing an active ingredientincompatible with the gelled outer phase, wherein the inner phasecontaining the active ingredient is encapsulated by the intermediatephase.

DETAILED DESCRIPTION OF THE INVENTION

An emulsion according to the present invention therefore alleviates theproblem described above, in that the intermediate phase separates theaqueous gelled outer phase from the active ingredients present in theaqueous inner phase.

Aptly the gelled outer phase comprises one or more gelled anionichydrocolloids. A frequently employed hydrocolloid in the presentinvention is gellan gum, other suitable hydrocolloids being alginates,pectins, carrageenans, agar, locust bean gum and the like.

Gellan gum refers to the extracellular polysaccharide obtained by theaerobic fermentation of the microorganism, Pseudomonas elodea, in asuitable nutrient medium. Various forms of gellan gum are known e.g.,native, deacetylated, deacetylated clarified, partially deacetylated,and partially deacetylated clarified.

It is preferred that the gellan gum employed in the present gel is a"low acetyl" gellan gum. As used herein, the term "low acetyl" denotes alevel of acylation of the gellan gum of 0.3 to 0% by weight.

Various alginates useful in this invention are described in detail by I.W. Cottrell and P. Kovacs in "Alginates," as Chapter 2 of Davidson, ed.,Handbook of Water-Soluble Gums and Resins (1980).

Alginates include "bioalgin" and "algal" alginate.

Biolalgin is microbially produced polysaccharides produced by bothPseudomonas and Azotobacter Strains as described, for example, in Jarmanet al., U.S. Pat. No. 4,235,966. These alginates are polysaccharidesconsisting of a partially acetylated variable block copolymer ofD-mannuronic and L-guluronic acid residues. iarman et al. state that thepolysaccharide produced is similar to that produced from seaweed exceptthat the molecule is partially acetylated.

The term "algal" alginate refers to naturally derived alginic acid andsalts thereof. Naturally derived aiginic acid, derived primarily fromkelp, is a commercially available product, e.g., KELACID™ (Kelco Div.,formerly Merck & Co., Inc., now acquired by Monsanto Company). The saltsinclude appropriate metal salts, e.g. alkali metal, alkaline earthmetal, ammonium salts, and organic derivatives, e.g. alkylene glycol,propylene glycol and the like. The preferred salts are sodium,potassium, magnesium, ammonium and propylene glycol algal alginate. Mostpreferred herein are naturally derived algal sodium alginates, such asthose sold commercially under the trademarks KELTEX, KELGIN and KELTONE™by Kelco Division formerly Merck & Co., Inc., now Monsanto Company.

Pectins are plant cell wall polysaccharides comprising branchedmolecules that contain many negatively charged galacturonic acidresidues. In view of their negative charge pectins are highly hydratedand readily bind to cations so as to be suitable for forming the gelledouter phase of the emulsion of the present invention.

Locust bean gum is an extract of the locust bean or carob, Ceratoniasiliqua. It is commercially available and is often used as a stabilizerin foods such as ice cream, sausages, and cheese.

It is preferred that the anionic hydrocolloid is present in the gelledouter phase in an amount of 0.1 to 5% by weight, based on the weight ofthe outer phase, for example 0.25 to 2.5% by weight. In the case wherean abradable gelled outer phase is required, for example in the casewhere the emulsion is for use as an antiperspirant, the hydrocolloid istypically present in an amount of 0.75 to 1.25% by weight, based on theweight of the outer phase. Alternatively for applications such as drugrelease systems, wherein the gelled phase is required to be erodiblewhen in contact with body fluids, the anionic hydrocolloid is typicallypresent in an amount of 0.5 to 0.6% by weight of the outer gelled phase.

Optionally the outer phase may, in some applications of the emulsionaccording to the present invention, such as for antiperspirants, bodylotions and the like, further contain a fragrance which may typically bepresent in an amount of 0.75 to 1.25% by weigh, based on the weight ofthe outer phase. The outer phase may contain colourant if desired.

The gelled outer phase may also optionally contain a preservative, apreferred preservative being n-propyl p-hydroxybenzoate. Thepreservative is suitably employed in a minor amount, such as not greaterthan about 0.2% by weight of the gelled outer phase.

Optionally the gelled outer phase may further contain a biocide,typically present in an amount of 0.05 to 2.5% by weight based on theweight of the outer phase.

Suitably one or more surfactants are also included in the outer phase,examples of suitable surfactants comprising diethanolamide cetylphosphate, polyoxyethylene castor oil, polyoxyethylene hydrogenatedcastor oil, polyoxyethylene triglycerides, polyoxyethylene lanolin,polyoxyethylene laurates, polyoxyethylene stearates and the like.Generally the surfactant is present in the outer phase at a level of 1to 3% by weight, based on the weight of the outer phase, more preferablythe surfactant is present at a level of 1.5 to 2.5% by weight, based onthe weight of the outer phase.

The anionic hydrocolloid may typically be gelled by a suitable cationsuch as calcium, magnesium or the like.

In the case of such multivalent gelling cations, these cations aresuitably provided by salts such as calcium chloride, magnesium chloride,calcium sulphate, magnesium sulphate and the like. The gellingmultivalent cations are generally present in the outer phase of theemulsion at a level not greater than 0.05% by weight, based on theweight of the outer phase.

In the case where the anionic hydrocolloid comprises gellan gum, it ispreferred that monovalent cations such as sodium, potassium and the likeare employed to gel the gellan gum, potassium being particularlypreferred. Aptly the monovalent cations are provided by a suitable saltsuch as sodium chloride, potassium chloride, trisodium citrate,tripotassium citrate and the like; in the case of potassium a preferredsalt is tripotassium citrate.

Advantageously the gelling monovalent cations are present in the outerphase at a level not greater than 0.5% by weight, based on the weight ofthe outer phase.

In the case where monovalent gelling cations are employed it ispreferred that the outer phase is essentially free of multivalent ions,such as calcium, magnesium or the like. The skilled worker willappreciate that it is most unusual to avoid gelling quantities ofmultivalent ions in this way since it is normal practice in the art touse multivalent ions to increase gel strength.

Desirably the non-aqueous intermediate phase comprises an oil phasewhich can comprise volatile silicone oils, petroleum, paraffin, orvegetable oil such as olive oil, arachis oil, castor oil, cottonseed orrapeseed oil or the like. In this way, there is provided by the presentinvention a triple phase emulsion of a water in oil emulsion dispersedin a water phase. A favoured oil phase in the present inventioncomprises a silicone oil, preferably a volatile silicone oil, althoughit is of course appreciated that the other above-mentioned oils cansimilarly be employed in the intermediate phase.

As hereinbefore described, an aim of the present invention is toencapsulate within a non-aqueous phase, an inner aqueous phasecontaining active ingredients incompatible with the gelled outer phase.

Aptly the active ingredients comprise cationic materials which areincompatible with anionic hydrocolloid gels in that the former wouldeffect degradation or precipitation of the latter.

Examples of such cationic materials include polyvalent metal ions,typically present as salts such as aluminium and/or zirconium salts,typically aluminium chlorohydrate, aluminium-zirconium chlorohydrate andthe like, cationic drugs such as verapamil hydrochloride,chloropheniramine maleate and the like, and cationic surfactants such asbenzalkonium chlorides, cetyl trimethyl ammonium chloride, lauryldimethyl ammonium chloride and the like.

It can be appreciated from the above range of active cationicingredients that an emulsion according to the present invention hasseveral applications.

In a first embodiment wherein the active cationic ingredient includesaluminium ions, the emulsion according to the present invention hasapplications as an antiperspirant; such antiperspirants containingaluminium ions were not previously prepared because of theincompatibility of aluminium containing materials with gels such as theanionic hydrocolloids suitable for use in the present invention.

In a second embodiment of the present invention wherein cationic drugsare present in the aqueous inner phase encapsulated by the intermediateoil phase, the emulsion of the present invention is useful as asustained release drug system wherein the outer gel phase is slowlyerodible when in contact with bodily fluids so as to release theencapsulated drugs.

In a further embodiment of the invention wherein the active ingredientscomprise cationic surfactants, personal hygiene products, such as bodylotions, moisturisers, creams and the like, can be provided by thepresent invention. The provision of such personal hygiene productsemploying an emulsion according to the present invention is desirable inthat a combination of the well known moisturising properties of water inoil emulsions and the desirable skin feel properties of oil in wateremulsions is achieved.

Aptly the inner phase comprises an aqueous solution of the activeingredient, wherein the solvent typically comprises water. The activeingredient is desirably present up to its limit of solubility, and inthe case where aluminium chlorohydrate (which is a favoured ingredient)is employed as the active ingredient the former can be included in anamount of up to 80% by weight, based on the weight of the inner phase.It can be appreciated that the inclusion of the active ingredient up toits limit of solubility in the solvent of the aqueous phase isbeneficial in allowing quantities of the active ingredient, which wouldotherwise be incompatible with the gelled outer phase, to beincorporated in the emulsion of the present invention.

Preferably a primary emulsion is initially formed wherein the aqueoussolution of the active ingredient is dispersed within the non-aqueousphase. Desirably 45 to 85% by weight of the aqueous solution isdispersed in 15 to 55% by weight of the non-aqueous phase. Suitable 55to 85% by weight of the primary emulsion is subsequently dispersedwithin a percentage balance by weight of an aqueous dispersion of agellable material, such as gellan gum or the like.

A hydrophobic surfactant is generally included in the non-aqueous phase.Examples of suitable surfactants include cetyl dimethicone copolyol,polysorbate 60, sorbitan monolaurate, sorbitan monostearate, sorbitanmono-oleate, sorbitan monopalmate, sorbitan trioleate, polyethyleneglycol-6-sorbitan beeswax, polyethylene glycol-20-sorbitan beeswax,ceteth-20-stearateath-2-steareath-20-oleath-2, aluminium magnesiumhydroxidestearate and the like. Typically the surfactant is present at alevel of 0.5 to 2.5% by weight, based on the weight of the non-aqueousphase. In the case where polysorbate 60 is employed, this surfactant isgenerally included at a level of 1.5 to 2.5% by weight, whereas cetyldimethicone copolyol is typically employed at a level of 0.5 to 1.5% byweight.

A particularly preferred emulsion according to the present inventioncomprises an outer gelled phase comprising gellan gum, typically gelledby monovalent ions substantially as hereinbefore described, anintermediate phase comprising silicone oil and an aqueous inner phasecontaining an active cationic ingredient particularly aluminiumchlorohydrate or aluminium-zirconium chlorohydrate. This particularlypreferred emulsion is suitable for use as antiperspirant and there isfurther provided by the present invention an anti-perspirant whichcomprises an emulsion comprising an outer gelled phase comprising gellangum, an intermediate phase comprising silicone oil and an aqueous innerphase containing an active cationic ingredient selected from the groupconsisting of aluminium chlorohydrate and aluminium-zirconiumchlorohydrate, wherein the inner phase containing the active cationicingredient is encapsulated by the intermediate phase.

An anti-perspirant according to the present invention is generally a"stick" type anti-perspirant, whereby the emulsion is substantiallysolid. A "stick" type anti-perspirant as described herein typicallycomprises a substantially solid body of an emulsion according to thepresent invention configured to be received within a container, wherebythe body is movable relative to the container between advanced andretracted positions.

There is still further provided by the present invention use of ananionic hydrocolloid substantially as hereinbefore described to providea gelled outer phase of an emulsion, wherein the emulsion comprises agelled outer phase comprising the anionic hydrocolloid, an intermediatenon-aqueous phase and an aqueous inner phase containing an activeingredient incompatible with the gelled outer phase, whereby the innerphase containing the active ingredient is encapsulated by theintermediate phase.

There is further provided by the present invention a method of preparingan emulsion substantially as hereinbefore described, which methodcomprises dispersing, in a non-aqueous phase, an aqueous phasecontaining an active ingredient, so as to produce a primary two phaseemulsion, mixing the primary emulsion with an aqueous dispersion of agellable material and effecting gelation thereof.

Aptly the gellable material comprises one or more anionic hydrocolloidssubstantially as hereinbefore described, wherein the employ of gellangum is particularly preferred. Similarly the non-aqueous phase and theactive ingredient are substantially as hereinbefore described, whereinpreferably the non-aqueous phase comprises a volatile silicone oil andthe active ingredient comprises a cationic material incompatible withthe anionic hydrocolloid.

Desirably a hydrophobic surfactant, such as cetyl dimethicone copolyolas described above, is intimately mixed with the non-aqueous phase priorto dispersal of the first mentioned aqueous phase therein. The employ ofsuch a surfactant is beneficial in achieving stabilisation of theprimary two phase emulsion.

Advantageously the non-aqueous phase is initially subjected torelatively low energy and shear agitation, typically employing astirrer, such as a paddle stirrer or the like, stirring at a speed inthe range of 350 to 450 rpm (preferably 390 to 410 rpm), during additionof the aqueous phase thereto.

Subsequently agitation of relatively high energy and shear is employed,typically stirring at a speed in the range of 1400 to 1600 rpra,preferably 1480 to 1520 rpm, whereby a stable primary emulsion isformed.

Typically the primary emulsion is heated to a temperature in the rangeof 50° to 60° C. prior to mixing with an aqueous dispersion of agellable material.

Suitably the method involves dispersing a gellable material, typicallythe anionic hydrocolloid as hereinbefore described, in an aqueouscarrier such as water, prior to mixing with the primary emulsion. Theresulting aqueous dispersion is generally heated to a temperature in therange of 80 to 90° C. to effect hydration followed by addition of DEAcetyl phosphate or other similar surfactant as hereinbefore described.Aptly the dispersion is cooled to a temperature in the range of 50 to60° C. prior to mixing with the primary emulsion. Optionally the mixtureachieved on mixing the primary emulsion with the aqueous dispersion maybe subjected to further heating to a temperature in the range of 65 to70° C.

Gelation is desirably achieved by addition of gelling cations, typicallymonovalent ions such as potassium or sodium in the case where gellan gumis employed as the anionic hydrocolloid. Aptly the mixture is allowed tocool and set to form a gel. According to a preferred aspect of theinvention tripotassium citrate is employed.

The weight percentages of the aqueous and nonaqueous phases, gellingcations and the like is substantially as hereinbefore described.Similarly the method may optionally further include blendingingredients, such as a fragrance, preservative or the like, ashereinbefore described, with the aqueous dispersion of the gellablematerial.

The present invention will now be illustrated by the following examples,which are for illustrative purposes only.

Example

    ______________________________________                                                           % w/w                                                      ______________________________________                                        Part A                                                                        Polysorbate 60                                2.0                             Aluminium-zirconium chlorohydrate                                                                       49.0                                                (50% aqueous solution)                                                        Silicone oil                                   49.0                           Part B                                                                        Gellan gum                                         0.6                        Biocide (triclosan)                      2.0                                  Deionised water                             95.4                              Polyethoxylated hydrogenated                                                                                  2.0                                           castor oil (60 ethylene oxide                                                 groups)                                                                       ______________________________________                                    

Part A was prepared by initially blending the polysorbate 60 with thesilicone oil. The aluminiumzirconium chlorohydrate was subsequentlyslowly added (by burette) whilst stirring at 400 rpm (±5 rpm) using apaddle stirrer, followed by stirring at 1500 rpm for 3-4 minutes to forma primary water in oil emulsion. The resulting primary emulsion washeated to 55° C. prior to intimately mixing with Part B.

Part B was prepared by dispersing the gellan gum in water, heating to85° C. to effect hydration of the gellan gum, followed by addition ofthe polyethoxylated hydrogenated castor oil and biocide thereto andcooling to 55° C. for mixing with the primary emulsion of Part A.

50 parts by weight of the primary emulsion of Part A were mixed with 50parts by weight of Part B whilst stirring at 800 rpm, followed byheating to 65-70° C. 0.5 parts by weight of CaCl₂.6H₂ O (0.1M) wereadded to gel the gellan gum, whereby gelation occurred on cooling.

Example

    ______________________________________                                                         % w/w                                                        ______________________________________                                        Part A                                                                        Cetyl dimethicone copolyol                                                                       1.0                                                        Silicone oil                                20.0                              Aluminium chlorohydrate                                                                                        79.0                                         (50% aqueous solution)                                                        Part B                                                                        Gellan gum                                    1.0                             DEA cetyl phosphate                                                                                                 2.0                                     Biocide (triclosan)                                                                                                0.6                                      Deionised water                          96.4                                 ______________________________________                                    

Part A was prepared by dissolving the cetyl dimethicone copolyol in thesilicone oil. The aluminium chlorohydrate was subsequently slowly added(by burette) whilst stirring at 400 rpm (±5 rpm) using a paddle stirrer,followed by stirring at 1500 rpm for 3-4 minutes to form the primarywater in oil emulsion. The resulting primary emulsion was heated to 55°C. prior to intimately mixing with Part B.

Part B was prepared by dispersing the gellan gum in water, heating to85° C. to effect hydration of the gellan gum, followed by addition ofthe DEA cetyl phosphate and the biocide thereto and cooling to 55° C.for mixing with the primary emulsion of part A.

67 parts by weight of the primary emulsion of Part A were added to 33parts by weight of Part B, whilst stirring at 800 rpm, followed byheating to 65-70° C. Tripotassium citrate was added to gel the gellangum, whereby gelation occurred on cooling.

We claim:
 1. A W/O/W sustained release emulsion comprising an aqueousgelled outer phase comprising one or more anionic hydrocolloids in anamount of 0.1% to 5% by weight of the weight of the outer phase, anon-aqueous intermediate phase comprising an oil and an inner phasecontaining a cationic ingredient incompatible with the gelled outerphase, wherein the inner phase containing the active ingredient isencapsulated by the intermediate phase.
 2. An emulsion according toclaim 1, wherein the anionic hydrocolloids comprise gellan gum,alginate, pectins, carrageenans, agar, or locust bean gum.
 3. Anemulsion according to claim 2, wherein the anionic hydrocolloidcomprises gellan gum.
 4. An emulsion according to claim 3, wherein thegellan gum is gelled by monovalent cations.
 5. An emulsion according toclaim 4, wherein the non-aqueous intermediate phase comprises an oilphase comprising silicone oil.
 6. An emulsion according to claim 5,wherein the active ingredient comprises a cationic ingredientincompatible with the anionic hydrocolloid of the outer phase.
 7. Anantiperspirant comprising a W/O/W sustained release emulsion comprisinga gelled outer phase comprising gellan gum, an intermediate phasecomprising silicone oil and an aqueous inner phase containing an activecationic ingredient selected from the group consisting of aluminiumchlorohydrate and aluminium-zirconium chlorohydrate, wherein the innerphase containing the active cationic ingredient is encapsulated by theintermediate phase.
 8. A sustained release drug system comprising anemulsion according to any of claims 1, 2 or 3-6, comprising a cationicdrug in an aqueous inner phase encapsulated by an intermediate oilphase, dispersed in an outer gel phase which is erodible when in contactwith body fluids to release said encapsulated drug.
 9. A personalhygiene product comprising an emulsion according to any of claims 1, 2or 3-6, wherein the active ingredient comprises cationic surfactants,moisturizers or creams.
 10. A method of preparing an emulsion accordingto any of claims 1, 2 or 3-6, which method comprises dispersing, in anon-aqueous phase, an aqueous phase containing an active ingredient, soas to produce a primary emulsion, mixing the primary emulsion with anaqueous dispersion of a gellable material and effecting gelationthereof.
 11. A method according to claim 10, wherein 45 to 85% by weightof an aqueous solution of the active ingredient is dispersed in 15 to55% by weight of the non-aqueous phase to form the primary emulsion, and55 to 85% by weight of the primary emulsion is subsequently dispersedwithin a percentage balance by weight of the aqueous dispersion of thegellable material.